Clinical risk factors associated with radiographic osteoarthritis progression among people with knee pain: a longitudinal study.

BACKGROUND: The aim of this study was to identify modifiable clinical factors associated with radiographic osteoarthritis progression over 1 to 2 years in people with painful medial knee osteoarthritis. METHODS: A longitudinal study was conducted within a randomised controlled trial, the "Long-term Evaluation of Glucosamine Sulfate" (LEGS study). Recruitment occurred in 2007-2009, with 1- and 2-year follow-up assessments by blinded assessors. Community-dwelling people with chronic knee pain (≥4/10) and medial tibiofemoral narrowing (but retaining >2mm medial joint space width) on radiographs were recruited. From 605 participants, follow-up data were available for 498 (82%, mean [sd] age 60 [8] years). Risk factors evaluated at baseline were pain, physical function, use of non-steroidal anti-inflammatory drugs (NSAIDs), statin use, not meeting physical activity guidelines, presence of Heberden's nodes, history of knee surgery/trauma, and manual occupation. Multivariable logistic regression analysis was conducted adjusting for age, sex, obesity, high blood pressure, allocation to glucosamine and chondroitin treatment, and baseline structural disease severity (Kellgren and Lawrence grade, joint space width, and varus alignment). Radiographic osteoarthritis progression was defined as joint space narrowing ≥0.5mm over 1 to 2 years (latest follow-up used where available). RESULTS: Radiographic osteoarthritis progression occurred in 58 participants (12%). Clinical factors independently associated with radiographic progression were the use of NSAIDs, adjusted odds ratios (OR) and 95% confidence intervals (CI) 2.05 (95% CI 1.1 to 3.8), and not meeting physical activity guidelines, OR 2.07 (95% CI 0.9 to 4.7). CONCLUSIONS: Among people with mild radiographic knee osteoarthritis, people who use NSAIDs and/or do not meet physical activity guidelines have a greater risk of radiographic osteoarthritis progression. TRIAL REGISTRATION: ClinicalTrials.gov , NCT00513422 . This original study trial was registered a priori, on August 8, 2007. The current study hypothesis arose before inspection of the data.

Glucosamine and chondroitin for knee osteoarthritis: a double-blind randomised placebo-controlled clinical trial evaluating single and combination regimens.

OBJECTIVE: To determine if the dietary supplements, glucosamine and/or chondroitin, result in reduced joint space narrowing (JSN) and pain among people with symptomatic knee osteoarthritis. METHODS: A double-blind randomised placebo-controlled clinical trial with 2-year follow-up. 605 participants, aged 45-75 years, reporting chronic knee pain and with evidence of medial tibio-femoral compartment narrowing (but retaining >2 mm medial joint space width) were randomised to once daily: glucosamine sulfate 1500 mg (n=152), chondroitin sulfate 800 mg (n=151), both dietary supplements (n=151) or matching placebo capsules (n=151). JSN (mm) over 2 years was measured from digitised knee radiographs. Maximum knee pain (0-10) was self-reported in a participant diary for 7 days every 2 months over 1 year. RESULTS: After adjusting for factors associated with structural disease progression (gender, body mass index (BMI), baseline structural disease severity and Heberden's nodes), allocation to the dietary supplement combination (glucosamine-chondroitin) resulted in a statistically significant (p=0.046) reduction of 2-year JSN compared to placebo: mean difference 0.10 mm (95% CI 0.002 mm to 0.20 mm); no significant structural effect for the single treatment allocations was detected. All four allocation groups demonstrated reduced knee pain over the first year, but no significant between-group differences (p=0.93) were detected. 34 (6%) participants reported possibly-related adverse medical events over the 2-year follow-up period. CONCLUSIONS: Allocation to the glucosamine-chondroitin combination resulted in a statistically significant reduction in JSN at 2 years. While all allocation groups demonstrated reduced knee pain over the study period, none of the treatment allocation groups demonstrated significant symptomatic benefit above placebo. TRIAL REGISTRATION CLINICALTRIALSGOV IDENTIFIER: NCT00513422; http://www.clinicaltrials.gov.

Arsenolipids in oil from blue whiting Micromesistius poutassou--evidence for arsenic-containing esters.

Arsenic-containing lipids in the oil from the blue whiting fish (Micromesistius poutassou) were separated into three broad polarity groups and investigated by HPLC and mass spectrometry. A total of 11 arsenolipids including 4 new compounds were identified. The polar lipid fraction constituting 24% of the total arsenolipid content (which totalled 2.16 µg As/g) contained four known dimethylarsinoyl fatty acids and three known dimethylarsinoyl hydrocarbons. The less polar fraction (ca 30% of the total arsenolipids) contained four new dimethylarsinoyl hydrocarbons with chain lengths 22-30 carbons, in addition to more complex arsenicals that hydrolysed to known dimethylarsinoyl fatty acids suggesting they were conjugated carboxylic acids, presumably esters. The rest of the lipid-soluble arsenic (ca 45% of the total) remained in the non-polar fraction together with the bulk of the fish oil lipids, a complex mixture of compounds that precluded identification of the small amounts of arsenolipids.

Reliability and longitudinal validity of computer-assisted methods for measuring joint damage progression in subjects with rheumatoid arthritis.

OBJECTIVE: To compare the metric properties of a computer-assisted erosion segmentation volume measurement with scoring using the Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) in a longitudinal cohort of patients with rheumatoid arthritis (RA). METHODS: Thirty-two sets of baseline and 2-year followup magnetic resonance imaging (MRI) of metacarpal phalangeal 2-5 joints of patients with RA were scored using RAMRIS and segmented using OSIRIS software. The smallest detectable difference (SDD), standardized response mean (SRM), and paired t-test were used to evaluate the sensitivity to change. Eleven of the 32 patients' MRI were segmented by both readers to evaluate interreader agreement. The 28-joint Disease Activity Score (DAS28) and Sharp erosion scores further evaluated construct and longitudinal validity. RESULTS: Reliability of erosion progression by computer-assisted volume measurement was superior to RAMRIS [intrareader interclass correlation coefficient (ICC) 0.97 (0.94-0.99) vs 0.52 (0.22-0.73)] and interreader ICC of volume measurement was 0.85 (0.53-0.96). Computer-assisted volume measurements identified 10 of 32 patients who progressed more than the SDD progression, whereas RAMRIS identified only 4 of 32 patients (p = 0.0013). By a paired t-test, however, all MRI measures progressed significantly over 2 years (irrespective of treatment arm) and there was little difference by SRM. Construct correlational validity of the MRI methods was 0.47-0.90 for status scores and 0.33-0.81 for progression. There was no relationship between the average DAS28 and erosion progression by any imaging method. CONCLUSION: Computer-assisted measurement of erosion volume has good performance metrics. It had excellent intrareader and interreader reliability and was more sensitive to change than RAMRIS in this group of patients. www.ClinicalTrials.gov, NCT00451971.

Optimizing physician handover through the creation of a comprehensive minimum data set.

Handover is defined as the communication of information between individuals and teams of healthcare providers to support the transfer of patient care and maintain professional responsibility and accountability. Poor handovers are increasingly recognized as potentially dangerous for patient safety and are associated with adverse events. One suggested method to improve the timely and efficient exchange of clinical information at handover and to reduce discontinuities in care is through the use of a minimum data set (MDS). The objective of this study was to describe the process of developing a single comprehensive hospital-wide MDS, created through an analysis of current handover processes and customary information tools used to support physician handover (MDHO) at a large quaternary care pediatric academic health sciences centre. A 20-item questionnaire was administered in person to a senior resident or fellow on each of 49 services identified to objectively assess MDHO processes, including frequency, consistency, format, participants and duration, for each service. The presence, type, location, responsibility for updating and security characteristics of MDHO tools used to support MDHO were also analyzed. The MDHO tools currently in use were collected and analyzed to create a comprehensive cross-institutional MDS. The analysis indicates that MDHO is highly consistent in terms of frequency, processes, participants, duration and the use of written tools to guide information exchange across departments. However, many best practice recommendations for MDHO are not being followed. Further, many of the existing MDHO tools in use have a similar content structure and already contain a majority of the components of a comprehensive MDS. Current local consistency in practice will allow for improved acceptance and adoption of an MDHO tool that continues to meet the clinical and administrative needs of physicians but also addresses needs for data accuracy and security. These additional specifications can be met through the use of information communication technologies.

Arsenic-containing lipids are natural constituents of sashimi tuna.

Arsenic occurs naturally in many types of seafood as water- and fat-soluble organoarsenic compounds. Although water-soluble compounds have been well characterized, the fat-soluble compounds, so-called arsenolipids, have until recently remained unknown. We report that sashimi-grade tuna fish, with a total arsenic content of 5.9 microg of As/g dry mass, contains approximately equal quantities of water- and fat-soluble arsenic. The water-soluble arsenic comprised predominantly arsenobetaine (>95%) with a trace of dimethylarsinate. Two fat-soluble compounds, which together accounted for about 40% of the lipid-arsenic, were isolated and characterized. The first was identified as 1-dimethylarsinoylpentadecane [(CH(3))(2)As(O)(CH(2))(14)CH(3)] by comparison of HPLC/mass spectrometric data and accurate mass data with those of an authenticated synthesized standard. The second arsenolipid was postulated as 1-dimethylarsinoyl all-cis-4,7,10,13,16,19-docosahexane from mass spectrometric data and analogy with non-arsenic-containing lipids found in fish. The remaining fat-soluble arsenic consisted of less polar arsenolipids of currently unknown structure. This is the first identification of arsenolipids in commonly consumed seafood.

Identification of arsenolipids with GC/MS.

Arsenic-containing hydrocarbons have recently been reported as natural constituents of fish oil. We report a simple method for determining these compounds by GC/MS. Application of the methodology will delineate the distribution of these novel arsenic compounds in foods, and facilitate an assessment of the toxicological implications.

Arsenic-containing hydrocarbons: natural compounds in oil from the fish capelin, Mallotus villosus.

Arsenic-containing hydrocarbons have been identified for the first time as natural components of fish oil.

Degradation of arylarsenic compounds by microorganisms.

Microorganisms were not directly accumulated when soil contaminated to about 0.5 mM with diphenylarsinic acid (DPAA) was used as the sole source of carbon. However, using toluene as the carbon source yielded several isolates, which were then used in cultivation with DPAA as the sole source of carbon. By these methods, Kytococcus sedentarius strain NK0508, which can grow in up to 0.038 mM DPAA, was isolated. The toxicity of DPAA retarded the growth of K. sedentarius and the direct accumulation of DPAA-utilizing microorganisms from environmental samples. This strain can utilize about 80% of DPAA and phenylarsonic acid as the sole source of carbon for 3 days. Degradation products of DPAA were determined to be cis, cis, muconate and arsenic acid. When K. sedentarius was cultivated with methylphenylarsinic acid and diphenylmethylarsine, about 90% and 10% degradation of the two compounds, respectively, were observed. Diphenylmethylarsine oxide, possibly synthesized by methylation of DPAA, was detected as one of the transformation products. These results suggest that degradation is initiated by splitting of the phenyl groups from the arylarsenic compounds with subsequent hydroxylation of the phenyl groups and ring opening to yield cis, cis, muconate.

The OMERACT Magnetic Resonance Imaging Inflammatory Arthritis Group - advances and priorities.

This article updates the work and research priorities of the OMERACT working group on magnetic resonance imaging (MRI) in inflammatory arthritis, as presented to the OMERACT 8 meeting in Malta in May 2006. This work focused on testing the reliability of dedicated extremity MRI in rheumatoid arthritis and on the initial steps in the development of an MRI score for peripheral psoriatic arthritis.

A multireader reliability study comparing conventional high-field magnetic resonance imaging with extremity low-field MRI in rheumatoid arthritis.

The use of extremity low-field magnetic resonance imaging (E-MRI) is increasing, but relatively few data exist on its reproducibility and accuracy in comparison with high-field MRI, especially for multiple readers. The aim of this multireader exercise of rheumatoid arthritis wrist and metacarpophalangeal joints was to assess the intermachine (high vs low-field) agreement and to assess the interreader agreement on high and low-field images. Study findings suggested that E-MRI performs similarly to conventional high-field MRI regarding assessment of bone erosions. However, for synovitis and bone edema, considerable intermachine and interreader variability was found. Further studies are needed before recommendations on multireader E-MRI assessment of these pathologies can be given.

A multicenter reliability study of extremity-magnetic resonance imaging in the longitudinal evaluation of rheumatoid arthritis.

There are limited data on the reliability of extremity magnetic resonance imaging (E-MRI) in the longitudinal evaluation of rheumatoid arthritis (RA). Our aim was to assess the interreader reliability of the OMERACT RA MRI score in the assessment of change in disease activity and bone erosion scores using 0.2 T E-MRI hand and wrist images from 2 timepoints, evaluated by 3 readers at different international centers. The intraclass correlation coefficients and smallest detectable difference results for the change scores were generally good for erosions and synovitis, but were not acceptable for bone edema. Overall, E-MRI demonstrated ability to detect change comparable to that reported for high-field MRI for erosion and synovitis.

Physical activity for osteoarthritis management: a randomized controlled clinical trial evaluating hydrotherapy or Tai Chi classes.

OBJECTIVE: To determine whether Tai Chi or hydrotherapy classes for individuals with chronic symptomatic hip or knee osteoarthritis (OA) result in measurable clinical benefits. METHODS: A randomized controlled trial was conducted among 152 older persons with chronic symptomatic hip or knee OA. Participants were randomly allocated for 12 weeks to hydrotherapy classes (n = 55), Tai Chi classes (n = 56), or a waiting list control group (n = 41). Outcomes were assessed 12 and 24 weeks after randomization and included pain and physical function (Western Ontario and McMaster Universities Osteoarthritis Index), general health status (Medical Outcomes Study Short Form 12 Health Survey [SF-12], version 2), psychological well-being, and physical performance (Up and Go test, 50-foot walk time, timed stair climb). RESULTS: At 12 weeks, compared with controls, participants allocated to hydrotherapy classes demonstrated mean improvements (95% confidence interval) of 6.5 (0.4, 12.7) and 10.5 (3.6, 14.5) for pain and physical function scores (range 0-100), respectively, whereas participants allocated to Tai Chi classes demonstrated improvements of 5.2 (-0.8, 11.1) and 9.7 (2.8, 16.7), respectively. Both class allocations achieved significant improvements in the SF-12 physical component summary score, but only allocation to hydrotherapy achieved significant improvements in the physical performance measures. All significant improvements were sustained at 24 weeks. In this almost exclusively white sample, class attendance was higher for hydrotherapy, with 81% attending at least half of the available 24 classes, compared with 61% for Tai Chi. CONCLUSION: Access to either hydrotherapy or Tai Chi classes can provide large and sustained improvements in physical function for many older, sedentary individuals with chronic hip or knee OA.

Seronegative spondyloarthropathy--studies from the Asia Pacific region.

Recent therapeutic advances, in particular the use of anti-tumour necrosis factor (anti-TNF) agents, have revived interest in the seronegative spondyloarthropathies (SpA), a group of arthritides characterised by axial skeletal involvement and the absence of rheumatoid factor. The purpose of this article is to review the studies that have been done in the Asia Pacific region, as a broad understanding of the scope and severity of this group of diseases would enable rheumatologists and physicians in this part of the world to better manage their patients. The majority of genetic studies have focused on the associations of HLA-B27 with ankylosing spondylitis (AS) and SpA, while a few studies examined the associations of the CARD, IL-1, LMP2, TAP and TGF with AS. There are a handful of studies on the immunological responses to bacteria and cytokine levels in AS. The onset and clinical features of SpA have been reported from most countries in the region, but no data on patient outcomes, using current measurement tools such as the Bath Ankylosing Spondylitis Disease Activity index (BASDAI), is available. Validation of these instruments of measurement as well as classification criteria in different ethnic populations is necessary where no prior data exist. Future studies will likely be focused on better clinical characterisation of patient cohorts, particularly with regard to the use of currently used measurement tools for disease activity and spinal function and mobility, and the identification of the need for biologic therapy in each country.

Power Doppler ultrasound in musculoskeletal disease: a systematic review.

OBJECTIVE: To evaluate the performance characteristics of power Doppler ultrasound as a diagnostic and monitoring tool in the assessment of musculoskeletal disease through a systematic review of the literature. SEARCH STRATEGY: We performed a literature search of PUBMED (1966 to June 2005). SELECTION CRITERIA: Only original research reports written in English involving musculoskeletal disease and power Doppler ultrasound were included. Reviews were noted but not included. Data Extraction/Reporting: The design, subjects, methods, imaging protocols, and performance characteristics studied in the research papers were reported. RESULTS: Of 3568 identified reports, 139 involved power Doppler ultrasound of the musculoskeletal system. Fifty-three of these reports met the inclusion criteria. Ultrasound machine settings were specified in 63% of reports. Rheumatoid arthritis was the most commonly studied musculoskeletal disease (64% of papers). Validity was the most studied performance characteristic (94% of reports), while reliability and responsiveness were studied in 17 and 34%, respectively. CONCLUSIONS: Although the majority of research reports of power Doppler ultrasound assessment of the musculoskeletal system evaluated validity, less than half reported reliability and responsiveness. Further work is needed to evaluate power Doppler ultrasound assessment of the musculoskeletal system before it can be used to guide clinical decisions or be used as an endpoint in clinical trials.

Very high concentrations of DDE and toxaphene residues in crocodiles from the Ord River, Western Australia: an investigation into possible endocrine disruption.

Organochlorine pesticide concentrations, particularly those of the DDT family and of toxaphene, were measured by gas chromatography in samples of liver and body fat taken from Australian freshwater crocodiles Crocodylus johnstoni at three locations along the Ord River in Western Australia. The three sampling sites were the irrigation area, downstream of the irrigation area, and well upstream of the irrigation area; the last site serving as the control. DDT and toxaphene were applied in large and known quantities to cotton grown in the Ord Irrigation Area from 1964 to 1974. Thus the residues in the crocodile tissues are representative of the situation almost thirty years after the use of DDT and toxaphene ceased in the area. Very high concentrations of p,p'-DDE and toxaphene were found in the lipid-rich tissues that were examined. Livers and body fat from estuarine crocodiles Crocodylus porosus from the downstream site were also analysed. As p,p'-DDE and toxaphene are both known to be disruptive of endocrine systems, a range of blood parameters, including estradiol and testesterone concentrations, were also measured for all the animals studied. The ovaries and testes of the freshwater crocodiles were also examined histologically. There were no obvious effects on blood chemistry or gonad histology of the large burden of pesticides and their metabolites carried by exposed animals, although the limited number of samples and the variability of the breeding state of the animals examined may have masked possible effects. The isolation of the area, the accurately known applications of DDT and toxaphene, and the simplicity of the drainage system make the lower Ord River a unique natural laboratory for studying the long term breakdown and effects of pesticides applied in a tropical environment.

Synovial membrane cytokine expression is predictive of joint damage progression in rheumatoid arthritis: a two-year prospective study (the DAMAGE study cohort).

OBJECTIVE: The primary aim of this prospective 2-year study was to explain the wide variability in joint damage progression in patients with rheumatoid arthritis (RA) from measures of pathologic changes in the synovial membrane. METHODS: Patients underwent clinical measurements and joint damage assessments by magnetic resonance imaging (MRI) and radiography at enrollment and at year 2. Synovial membrane was obtained by knee biopsy and assessed histologically by hematoxylin and eosin staining. Interleukin-1beta (IL-1beta), IL-10, IL-16, IL-17, RANKL, tumor necrosis factor alpha (TNFalpha), and interferon-gamma (IFNgamma) messenger RNA (mRNA) expression was determined by quantitative reverse transcription-polymerase chain reaction. The relationship of synovial measurements to joint damage progression was determined by multivariate analysis. RESULTS: Sixty patients were enrolled. Histologic features had no relationship to damage progression. Multivariate analysis by several different methods consistently demonstrated that synovial membrane mRNA levels of IL-1beta, TNFalpha, IL-17, and IL-10 were predictive of damage progression. IL-17 was synergistic with TNFalpha. TNFalpha and IL-17 effects were most pronounced with shorter disease duration, and IL-1beta effects were most pronounced with longer disease duration. IFNgamma was protective. These factors explained 57% of the MRI joint damage progression over 2 years. CONCLUSION: We have demonstrated for the first time in a prospective study that synovial membrane cytokine mRNA expression is predictive of joint damage progression in RA. The findings for IL-1beta and TNFalpha are consistent with results of previous clinical research, but the protective role of IFNgamma, the differing effects of disease duration, and IL-17-cytokine interactions had only been demonstrated previously by animal and in vitro research. These findings explain some of the variability of joint damage in RA and identify new targets for therapy.

Diastereoisomerism of thiol complexes of arsenic acids and pseudoasymmetry of arsenic: a 1H and 13C NMR study.

Diastereoisomeric complexes of methylphenylarsinic acid and (L)-glutathione could be partially separated by HPLC, but the separated compounds rapidly racemized, presumably by pyramidal inversion at the arsenic atom. Hydrolysis of the diastereoisomeric complexes yielded methylphenylarsinous acid as a pair of enantiomers revealed by a 1H NMR study with an asymmetric lanthanide shift reagent. Methylphenylarsinous acid was also synthesized as an enantiomeric pair, shown by an asymmetric shift reagent experiment, by the hydrolysis of iodomethylphenylarsine. 1H and 13C NMR spectroscopy were used to demonstrate that complexing of phenylarsonic acid with (R,S)-3-mercapto-1,2-propanediol and with (R,S)-1-mercapto-2-propanol yielded, in each case, a pair of enantiomers, PhAs[(R)-ligand)]2, PhAs[(S)-ligand)]2, in which the homomorphic ligands were diastereotopic, and a pair of diastereoisomers, PhAs[(R)-ligand][(S)-ligand], which differed from each other in the configuration about the pseudoasymmetric arsenic atom.

Aerial oxidation of the glucocorticoid side-chain under pH control.

The outcome of aerial oxidation of the glucocortico-steroid side-chain (as exemplified by dexamethasone) has been shown to be subject to strict pH control. At pH 7.4 the glyoxal is the only product; at pH values of 8 and 9.2 the etioacid is formed, and at pH values of 13 or above the epimeric glycolic acids are produced. The glycolic acid epimer that predominates by a factor of 2 and is more stable has been shown by an X-ray crystal structural analysis to be the 20R compound. The presence of arsenite changes the course of the reaction and only the glycolic acids are yielded at pH values of 8 and above.